Despite the high mortality and morbidity of lung diseases, they are frequently difficult to diagnose and phenotype, especially in the early, potentially better treatable stages. For childhood lung disease, the case becomes even more compelling because the primary imaging modalities for the lung expose the child to ionizing radiation, and children are more radiation sensitive than adults. Thus, hyperpolarized gas MRI might be particularly suitable to assess asthma, cystic fibrosis (CF), bronchopulmonary dysplasia (BPD) or pulmonary pathology in sickle cell patients in children. To this extent we propose to advance the methodology of Xenon polarization Transfer Contrast (XTC) MRI and the distribution capabilities of the required hyperpolarized xenon-129 (HXe129). XTC MRI in its current implementation can only characterize the gas exchange process between the lung tissue and the alveolar air spaces in general. However, we hypothesize that additional refinements and the use of magnetic field strengths up to 3 T will permit new spectral selectivity, distinguishing for the first time in humans exchange between the airspaces and parenchyma from exchange between the airspaces and red blood cells. Such an improvement would allow considerably higher sensitivity for pathological changes and better disease phenotyping. These efforts will be accomplished by temporarily relocating Xemed's portable clinical polarizer prototype to the Children's Hospital of Philadelphia. This demonstration of a cost-effective approach to meeting the scientific infrastructure requirements for hyperpolarized xenon MRI will lower the cost barrier to many research groups seeking to access a world-class xenon polarizer.Xenon polarization Transfer Contrast (XTC) MRI has been shown to be a promising tool to measure lung function through the detection of the ongoing gas- exchange processes between lung parenchyma and alveolar air spaces. In this proposal we suggest to extend the technique to monitor gas exchange between the air spaces and the two distinguishable dissolved-phase compartments, the red blood cells and the lung tissue itself, at 1.5 T and 3 T. Combining these advances with the availability of large quantities of highly polarized xenon-129 will permit the performance of a series of extremely targeted, non-invasive lung function tests, without employing ionizing radiation or radioactive tracers, that could be conducted within 5-6 6s breath holds. Since such maneuvers can usually be performed even by patients with severe lung disease or young children the resulting product would be of tremendous interest to the pharmaceutical industry for the development of novel drugs for pulmonary diseases and the monitoring of treatment over extended periods of time. [unreadable] [unreadable] [unreadable]